Krakow Centre for Medical Research and Technologies, John Paul II Hospital, Krakow, Poland; Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland.
Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland.
Thromb Res. 2018 Mar;163:12-18. doi: 10.1016/j.thromres.2018.01.004. Epub 2018 Jan 5.
Venous thromboembolism (VTE) is associated with hypofibrinolysis. Its mechanisms are poorly understood. We investigated plasminogen-fibrin interaction and its association with fibrinolytic capacity and protein oxidation/carbonylation in VTE patients.
Plasma-purified plasminogen conversion to plasmin and surface plasmon resonance employed for plasminogen-fibrin interactions were individually evaluated in all healthy controls and non-anticoagulated patients following VTE, 10-23months since the event. We also assessed plasma fibrin clot permeability (K), clot lysis time (LT), activators and inhibitors of fibrinolysis together with oxidation/carbonylation markers.
VTE patients had impaired plasminogen binding to fibrin (apparent Kd, +290%, p=0.002), reduced rate of plasmin generation (-4.7%, p=0.001), and longer LT (+18.6%, p<0.001) compared with controls. Fibrinogen and K were similar in both groups. Apparent Kd correlated with LT (r=0.43, p=0.037), tissue plasminogen activator-plasminogen activator inhibitor 1 (tPA-PAI-1) complexes (r=0.63, p=0.012), and active PAI-1 (r=0.49, p=0.03). Compared with controls, VTE patients had higher thiobarbituric acid reactive substances (TBARS), total protein carbonyl content (PC), and lower total antioxidant capacity (all p<0.001), that all were associated with LT (r=0.61, r=0.56, and r=-0.47, respectively, all p<0.05). Impaired plasminogen binding to fibrin reflected by apparent Kd positively correlated with TBARS (r=0.48, p=0.032) and PC (r=0.54, p=0.013) in the whole group.
Plasminogen-fibrin interactions are altered in young and middle-aged VTE patients, without known thrombophilias, except increased factor VIII. The mechanisms underlying these phenomena remain to be established.
静脉血栓栓塞症（VTE）与纤溶活性降低有关。其机制尚不清楚。我们研究了纤溶酶原与纤维蛋白的相互作用及其与 VTE 患者纤溶能力和蛋白氧化/羰基化的关系。
在所有健康对照者和非抗凝 VTE 患者中，分别评估了血浆纯化纤溶酶原转化为纤溶酶和表面等离子体共振的纤溶酶原与纤维蛋白的相互作用，这些患者在事件发生后 10-23 个月。我们还评估了血浆纤维蛋白凝块的通透性（K）、凝块溶解时间（LT）、纤溶的激活剂和抑制剂以及氧化/羰基化标志物。
与对照组相比，VTE 患者的纤溶酶原与纤维蛋白的结合能力受损（表观 Kd，增加 290%，p=0.002），纤溶酶的生成速度降低（-4.7%，p=0.001），LT 延长（+18.6%，p<0.001）。两组纤维蛋白原和 K 相似。表观 Kd 与 LT 相关（r=0.43，p=0.037）、组织型纤溶酶原激活物-纤溶酶原激活物抑制剂 1（tPA-PAI-1）复合物（r=0.63，p=0.012）和活性 PAI-1（r=0.49，p=0.03）。与对照组相比，VTE 患者的硫代巴比妥酸反应物质（TBARS）、总蛋白羰基含量（PC）更高，总抗氧化能力（TAC）更低（均 p<0.001），且均与 LT 相关（r=0.61，r=0.56，r=-0.47，均 p<0.05）。整个组中，表观 Kd 反映的纤溶酶原与纤维蛋白的结合能力受损与 TBARS（r=0.48，p=0.032）和 PC（r=0.54，p=0.013）呈正相关。
年轻和中年 VTE 患者的纤溶酶原与纤维蛋白的相互作用发生改变，除了因子 VIII 增加外，没有已知的血栓形成倾向。这些现象的机制尚待确定。
